Adrenoleukodystropy is an X-linked disorder that has variable manifestations including adrenal insufficiency, inflammatory demyelination of the brain, and in adults, a progressive spastic paraparesis. Interventions when begun prior to disease onset can be life saving and include monitoring for adrenal and cerebral disease;early, appropriate use of hematopoietic stem cell therapy;and experimental therapy with diet and Lorenzo's oil to reduce the incidence of childhood cerebral disease. Using the biochemical abnormality of elevated very long chain fatty acids, we have recently developed a tandem mass spectrometry methodology that can detect altered elevations in lysophospholipids. This methodology is adaptable to regional newborn screening of metabolic disorders offering early diagnosis and intervention in adrenoleukodystrophy and other peroxisomal disorders. In this proposal, we propose three aims to be completed in three years. We will optimize the methodology for adaptation to large-scale screening, confirm the sensitivity of the assay in 500 newborn blood samples with a known percentage of affected individuals, and the third phase is to complete an initial field trial in Maryland of 5000 samples to confirm the sensitivity and specificity. Successful completion of the three aims would establish this as a viable addition to newborn screening. PUBLIC HEALTH RELEVANCE: The public health importance of this proposal is that adrenoleukodystrophy is a serious disorder affecting children and adults with an incidence of approximately 1:20,000. Therapies, which have been developed, rely extensively on presymptomatic diagnosis and monitoring which unfortunately occurs in only a limited percentage of individuals. We propose to develop a methodology which can occur with standard regional newborn screening and confirm the sensitivity and specificity of the technique. Broader use of this optimized method should allow quicker diagnosis for families and maximum translation of recent therapeutic interventions.